Developing a comprehensive plan to achieve U.S. energy independence is the "single biggest" way to boost the economy, FedEx Chairman and CEO Fred Smith told CNBC on Wednesday.

"Oil is at the center of everything we do," Smith said in a "Squawk Box" interview. "If we produce more in the U.S. and use less and develop alternatives … you allow the United States within our economy a half a trillion dollars more in GDP."

Smith opened the OPEC Oil Embargo 40 summit, sponsored by Securing America's Future Energy, in Washington on Wednesday. He's the co-chair of the advocacy group's Energy Security Leadership Council of retired generals, admirals and CEOs of oil-using companies.

"When OPEC instituted the oil embargo 40 years ago … we were only importing about 35 percent of our oil," he said. "Withholding those oil supplies threw the U.S. economy into complete chaos." The U.S. now imports less than 40 percent, he added.

Less reliance on foreign oil "allows us the flexibility to conduct our international affairs and our foreign policy without regard to be hostage to these national oil companies," Smith said.

As Democrats and Republicans inch closer to a deal to increase the debt ceiling by the midnight deadline and reopen the government, Smith said the shutdown has "definitely had a minor effect on business" at FedEx. "Just as one example, we have tens of thousands of shipments held right now that we can't deliver to the U.S. government."

But he expressed optimism about the budget talks.

"I have confidence they'll come to a conclusion," he said. "Our system is tends to be pretty fractious but at the end of the day generally ends up in the right place."